RT Journal Article SR Electronic T1 Insulin and Fibroblast Growth Factor 2 Activate a Neurogenic Program in Müller Glia of the Chicken Retina JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 9387 OP 9398 DO 10.1523/JNEUROSCI.22-21-09387.2002 VO 22 IS 21 A1 Andy J. Fischer A1 Christopher Roger McGuire A1 Blair Dorian Dierks A1 Thomas A. Reh YR 2002 UL http://www.jneurosci.org/content/22/21/9387.abstract AB We have reported previously that neurotoxic damage to the chicken retina causes Müller glia to dedifferentiate, proliferate, express transcription factors common to retinal progenitors, and generate new neurons and glia, whereas the majority of newly produced cells remain undifferentiated (Fischer and Reh, 2001). Because damaged retinal cells have been shown to produce increased levels of insulin-related factors and FGFs, in the current study we tested whether intraocular injections of growth factors stimulate Müller glia to proliferate and produce new neurons. We injected growth factors and bromodeoxyuridine into the vitreous chamber of the eyes of chickens and assayed for changes in glial phenotype and proliferation within the retina. Although insulin or FGF2 alone had no effect, the combination of insulin and FGF2 caused Müller glia to coexpress transcription factors common to retinal progenitors (Pax6 and Chx10) and initiated a wave of proliferation in Müller cells that began at the retinal margin and spread into peripheral regions of the retina. Most of the newly formed cells remain undifferentiated, expressing Pax6 and Chx10, whereas some differentiate into Müller glia, and a few differentiate into neurons that express the neuronal markers Hu or calretinin. There was no evidence of retinal damage in eyes treated with insulin and FGF2. We conclude that the combination of insulin and FGF2 stimulated Müller glia to dedifferentiate, proliferate, and generate new neurons. These findings imply that exogenous growth factors might be used to stimulate endogenous glial cells to regenerate neurons in the CNS.